What Are Thalassemias?

Thalassemias (thal-a-SE-me-ahs) are inherited blood disorders. "Inherited" means that the
disorder is passed from parents to children through genes.
Thalassemias cause the body to make fewer healthy red blood cells and less hemoglobin
(HEE-muh-glow-bin) than normal. Hemoglobin is an iron-rich protein in red blood cells.
It carries oxygen to all parts of the body. Hemoglobin also carries carbon dioxide (a waste
gas) from the body to the lungs, where it's exhaled.
People who have thalassemias can have mild or severe anemia (uh-NEE-me-uh). Anemia
is caused by a lower than normal number of red blood cells or not enough hemoglobin in
the red blood cells.

Overview
Normal hemoglobin, also called hemoglobin A, has four protein chainstwo alpha
globin and two beta globin. The two major types of thalassemia, alpha and beta, are
named after defects in these protein chains.
Four genes (two from each parent) are needed to make enough alpha globin protein
chains. Alpha thalassemia trait occurs if one or two of the four genes are missing. If more
than two genes are missing, moderate to severe anemia occurs.
The most severe form of alpha thalassemia is called alpha thalassemia major or hydrops
fetalis. Babies who have this disorder usually die before or shortly after birth.
Two genes (one from each parent) are needed to make enough beta globin protein chains.
Beta thalassemia occurs if one or both genes are altered.
The severity of beta thalassemia depends on how much one or both genes are affected. If
both genes are affected, the result is moderate to severe anemia. The severe form of beta
thalassemia is known as thalassemia major or Cooley's anemia.
Thalassemias affect males and females. The disorders occur most often among people of
Italian, Greek, Middle Eastern, Southern Asian, and African descent. Severe forms
usually are diagnosed in early childhood and are lifelong conditions.
Doctors diagnose thalassemias using blood tests. The disorders are treated with blood
transfusions, medicines, and other procedures.

Outlook

Treatments for thalassemias have improved over the years. People who have moderate or
severe thalassemias are now living longer and have better quality of life.
However, complications from thalassemias and their treatments are frequent. People who
have moderate or severe thalassemias must closely follow their treatment plans. They
need to take care of themselves to remain as healthy as possible.

Other Names for Thalassemias

The various types of thalassemia have specific names related to the severity of the
disorder. (For more information about the types of thalassemia, go to "What Causes
Thalassemias?")

Alpha Thalassemias

Alpha thalassemia silent carrier

Alpha thalassemia minor, also called alpha thalassemia trait
Hemoglobin H disease
Alpha thalassemia major, also called hydrops fetalis

Beta Thalassemias

Beta thalassemia minor, also called beta thalassemia trait

Beta thalassemia intermedia
Beta thalassemia major, also called Cooley's anemia or beta-zero (0) thalassemia
Beta-plus (+) thalassemia
Mediterranean anemia

What Causes Thalassemias?

Your body makes three types of blood cells: red blood cells, white blood cells, and
platelets (PLATE-lets). Red blood cells contain hemoglobin, an iron-rich protein that
carries oxygen from your lungs to all parts of your body. Hemoglobin also carries carbon
dioxide (a waste gas) from your body to your lungs, where it's exhaled.
Hemoglobin has two kinds of protein chains: alpha globin and beta globin. If your body
doesn't make enough of these protein chains or they're abnormal, red blood cells won't
form correctly or carry enough oxygen. Your body won't work well if your red blood cells
don't make enough healthy hemoglobin.
Genes control how the body makes hemoglobin protein chains. When these genes are
missing or altered, thalassemias occur.

Thalassemias are inherited disordersthat is, they're passed from parents to children
through genes. People who inherit faulty hemoglobin genes from one parent but normal
genes from the other are called carriers. Carriers often have no signs of illness other than
mild anemia. However, they can pass the faulty genes on to their children.
People who have moderate to severe forms of thalassemia have inherited faulty genes
from both parents.

Alpha Thalassemias
You need four genes (two from each parent) to make enough alpha globin protein chains.
If one or more of the genes is missing, you'll have alpha thalassemia trait or disease. This
means that your body doesn't make enough alpha globin protein.

If you're only missing one gene, you're a "silent" carrier. This means you won't
have any signs of illness.
If you're missing two genes, you have alpha thalassemia trait (also called alpha
thalassemia minor). You may have mild anemia.
If you're missing three genes, you likely have hemoglobin H disease (which a
blood test can detect). This form of thalassemia causes moderate to severe
anemia.

Very rarely, a baby is missing all four genes. This condition is called alpha thalassemia
major or hydrops fetalis. Babies who have hydrops fetalis usually die before or shortly
after birth.

Example of an Inheritance Pattern for Alpha Thalassemia

The picture shows one example of how alpha thalassemia is inherited. The alpha globin
genes are located on chromosome 16. A child inherits four alpha globin genes (two from
each parent). In this example, the father is missing two alpha globin genes and the mother
is missing one alpha globin gene.
Each child has a 25 percent chance of inheriting two missing genes and two normal genes
(thalassemia trait), three missing genes and one normal gene (hemoglobin H disease),
four normal genes (no anemia), or one missing gene and three normal genes (silent
carrier).

Beta Thalassemias

You need two genes (one from each parent) to make enough beta globin protein chains. If
one or both of these genes are altered, you'll have beta thalassemia. This means that your
body wont make enough beta globin protein.

If you have one altered gene, you're a carrier. This condition is called beta
thalassemia trait or beta thalassemia minor. It causes mild anemia.
If both genes are altered, you'll have beta thalassemia intermedia or beta
thalassemia major (also called Cooley's anemia). The intermedia form of the
disorder causes moderate anemia. The major form causes severe anemia.

Example of an Inheritance Pattern for Beta Thalassemia

The picture shows one example of how beta thalassemia is inherited. The beta globin
gene is located on chromosome 11. A child inherits two beta globin genes (one from each
parent). In this example, each parent has one altered beta globin gene.
Each child has a 25 percent chance of inheriting two normal genes (no anemia), a 50
percent chance of inheriting one altered gene and one normal gene (beta thalassemia
trait), or a 25 percent chance of inheriting two altered genes (beta thalassemia major).

Who Is at Risk for Thalassemias?

Family history and ancestry are the two risk factors for thalassemias.

Family History
Thalassemias are inheritedthat is, the genes for the disorders are passed from parents to
their children. If your parents have missing or altered hemoglobin-making genes, you
may have thalassemia.

Ancestry
Thalassemias occur most often among people of Italian, Greek, Middle Eastern, Southern
Asian, and African descent.

What Are the Signs and Symptoms of

Thalassemias?

A lack of oxygen in the bloodstream causes the signs and symptoms of thalassemias. The
lack of oxygen occurs because the body doesn't make enough healthy red blood cells and
hemoglobin. The severity of symptoms depends on the severity of the disorder.

No Symptoms
Alpha thalassemia silent carriers generally have no signs or symptoms of the disorder.
The lack of alpha globin protein is so minor that the body's hemoglobin works normally.

Mild Anemia
People who have alpha or beta thalassemia trait can have mild anemia. However, many
people who have these types of thalassemia have no signs or symptoms.
Mild anemia can make you feel tired. Mild anemia caused by alpha thalassemia trait
might be mistaken for iron-deficiency anemia.

Mild to Moderate Anemia and Other Signs and

Symptoms
People who have beta thalassemia intermedia have mild to moderate anemia. They also
may have other health problems, such as:

Slowed growth and delayed puberty. Anemia can slow down a child's growth and
development.
Bone problems. Thalassemia may cause bone marrow to expand. Bone marrow is
the spongy substance inside bones that makes blood cells. When bone marrow
expands, the bones become wider than normal. They may become brittle and
break easily.
An enlarged spleen. The spleen is an organ that helps your body fight infection
and remove unwanted material. When a person has thalassemia, the spleen has to
work very hard. As a result, the spleen becomes larger than normal. This makes
anemia worse. If the spleen becomes too large, it must be removed.

Severe Anemia and Other Signs and Symptoms

People who have hemoglobin H disease or beta thalassemia major (also called Cooley's
anemia) have severe thalassemia. Signs and symptoms usually occur within the first
2 years of life. They may include severe anemia and other health problems, such as:

A pale and listless appearance

Poor appetite
Dark urine (a sign that red blood cells are breaking down)
Slowed growth and delayed puberty

Jaundice (a yellowish color of the skin or whites of the eyes)

An enlarged spleen, liver, or heart
Bone problems (especially with bones in the face)

Complications of Thalassemias
Better treatments now allow people who have moderate and severe thalassemias to live
much longer. As a result, these people must cope with complications of these disorders
that occur over time.

Heart and Liver Diseases

Regular blood transfusions are a standard treatment for thalassemias. Transfusions can
cause iron to build up in the blood (iron overload). This can damage organs and tissues,
especially the heart and liver.
Heart disease caused by iron overload is the main cause of death in people who have
thalassemias. Heart disease includes heart failure, arrhythmias (irregular heartbeats), and
heart attack.

Infection
Among people who have thalassemias, infections are a key cause of illness and the
second most common cause of death. People who have had their spleens removed are at
even higher risk because they no longer have this infection-fighting organ.

Osteoporosis
Many people who have thalassemias have bone problems, including osteoporosis (OS-teo-po-RO-sis). This is a condition in which bones are weak and brittle and break easily.

How Are Thalassemias Diagnosed?

Doctors diagnose thalassemias using blood tests, including a complete blood count
(CBC) and special hemoglobin tests.

A CBC measures the amount of hemoglobin and the different kinds of blood cells,
such as red blood cells, in a sample of blood. People who have thalassemias have
fewer healthy red blood cells and less hemoglobin than normal in their blood.
People who have alpha or beta thalassemia trait may have red blood cells that are
smaller than normal.
Hemoglobin tests measure the types of hemoglobin in a blood sample. People
who have thalassemias have problems with the alpha or beta globin protein chains
of hemoglobin.

Moderate and severe thalassemias usually are diagnosed in early childhood. This is
because signs and symptoms, including severe anemia, often occur within the first
2 years of life.
People who have milder forms of thalassemia might be diagnosed after a routine blood
test shows they have anemia. Doctors might suspect thalassemia if a person has anemia
and is a member of an ethnic group that's at increased risk for thalassemias. (For more
information, go to "Who Is at Risk for Thalassemias?")
Doctors also test the amount of iron in the blood to find out whether the anemia is due to
iron deficiency or thalassemia. Iron-deficiency anemia occurs if the body doesn't have
enough iron to make hemoglobin. The anemia in thalassemia occurs because of a
problem with either the alpha globin or beta globin chains of hemoglobin, not because of
a lack of iron.
Because thalassemias are passed from parents to children through genes, family genetic
studies also can help diagnose the disorder. These studies involve taking a family medical
history and doing blood tests on family members. The tests will show whether any family
members have missing or altered hemoglobin genes.
If you know of family members who have thalassemias and you're thinking of having
children, consider talking with your doctor and a genetic counselor. They can help
determine your risk for passing the disorder to your children.
If you're expecting a baby and you and your partner are thalassemia carriers, you may
want to consider prenatal testing.
Prenatal testing involves taking a sample of amniotic fluid or tissue from the placenta.
(Amniotic fluid is the fluid in the sac surrounding a growing embryo. The placenta is the
organ that attaches the umbilical cord to the mother's womb.) Tests done on the fluid or
tissue can show whether your baby has thalassemia and how severe it might be.

How Are Thalassemias Treated?

Treatments for thalassemias depend on the type and severity of the disorder. People who
are carriers or who have alpha or beta thalassemia trait have mild or no symptoms.
Theyll likely need little or no treatment.
Doctors use three standard treatments for moderate and severe forms of thalassemia.
These treatments include blood transfusions, iron chelation (ke-LAY-shun) therapy, and
folic acid supplements. Other treatments have been developed or are being tested, but
they're used much less often.

Standard Treatments

Blood Transfusions
Transfusions of red blood cells are the main treatment for people who have moderate or
severe thalassemias. This treatment gives you healthy red blood cells with normal
hemoglobin.
During a blood transfusion, a needle is used to insert an intravenous (IV) line into one of
your blood vessels. Through this line, you receive healthy blood. The procedure usually
takes 1 to 4 hours.
Red blood cells live only for about 120 days. So, you may need repeated transfusions to
maintain a healthy supply of red blood cells.
If you have hemoglobin H disease or beta thalassemia intermedia, you may need blood
transfusions on occasion. For example, you may have transfusions when you have an
infection or other illness, or when your anemia is severe enough to cause tiredness.
If you have beta thalassemia major (Cooley's anemia), youll likely need regular blood
transfusions (often every 2 to 4 weeks). These transfusions will help you maintain normal
hemoglobin and red blood cell levels.
Blood transfusions allow you to feel better, enjoy normal activities, and live into
adulthood. This treatment is lifesaving, but it's expensive and carries a risk of
transmitting infections and viruses (for example, hepatitis). However, the risk is very low
in the United States because of careful blood screening.
For more information, go to the Health Topics Blood Transfusion article.

Iron Chelation Therapy

The hemoglobin in red blood cells is an iron-rich protein. Thus, regular blood
transfusions can lead to a buildup of iron in the blood. This condition is called iron
overload. It damages the liver, heart, and other parts of the body.
To prevent this damage, doctors use iron chelation therapy to remove excess iron from
the body. Two medicines are used for iron chelation therapy.

Deferoxamine is a liquid medicine that's given slowly under the skin, usually with
a small portable pump used overnight. This therapy takes time and can be mildly
painful. Side effects include problems with vision and hearing.
Deferasirox is a pill taken once daily. Side effects include headache, nausea
(feeling sick to the stomach), vomiting, diarrhea, joint pain, and tiredness.

Folic Acid Supplements

Folic acid is a B vitamin that helps build healthy red blood cells. Your doctor may
recommend folic acid supplements in addition to treatment with blood transfusions
and/or iron chelation therapy.

Other Treatments
Other treatments for thalassemias have been developed or are being tested, but they're
used much less often.

Blood and Marrow Stem Cell Transplant

A blood and marrow stem cell transplant replaces faulty stem cells with healthy ones
from another person (a donor). Stem cells are the cells inside bone marrow that make red
blood cells and other types of blood cells.
A stem cell transplant is the only treatment that can cure thalassemia. But only a small
number of people who have severe thalassemias are able to find a good donor match and
have the risky procedure.
For more information, go to the Health Topics Blood and Marrow Stem Cell Transplant
article.

Possible Future Treatments

Researchers are working to find new treatments for thalassemias. For example, it might
be possible someday to insert a normal hemoglobin gene into stem cells in bone marrow.
This will allow people who have thalassemias to make their own healthy red blood cells
and hemoglobin.
Researchers also are studying ways to trigger a person's ability to make fetal hemoglobin
after birth. This type of hemoglobin is found in fetuses and newborns. After birth, the
body switches to making adult hemoglobin. Making more fetal hemoglobin might make
up for the lack of healthy adult hemoglobin.

Treating Complications
Better treatments now allow people who have moderate and severe thalassemias to live
longer. As a result, these people must cope with complications that occur over time.
An important part of managing thalassemias is treating complications. Treatment might
be needed for heart or liver diseases, infections, osteoporosis, and other health problems.

How Can Thalassemias Be Prevented?

You cant prevent thalassemias because theyre inherited (passed from parents to children
through genes). However, prenatal tests can detect these blood disorders before birth.
Family genetic studies may help find out whether people have missing or altered
hemoglobin genes that cause thalassemias. (For more information, go to "How Are
Thalassemias Diagnosed?")
If you know of family members who have thalassemias and you're thinking of having
children, consider talking with your doctor and a genetic counselor. They can help
determine your risk for passing the disorder to your children.

Living With Thalassemias

Survival and quality of life have improved for people who have moderate or severe
thalassemias. This is because:

More people are able to get blood transfusions now.

Blood screening has reduced the number of infections from blood transfusions.
Also, treatments for other kinds of infections have improved.
Iron chelation treatments are available that are easier for some people to take.
Some people have been cured through blood and marrow stem cell transplants.

Living with thalassemia can be challenging, but several approaches can help you cope.

Follow Your Treatment Plan

Following the treatment plan your doctor gives you is important. For example, get blood
transfusions as your doctor recommends, and take your iron chelation medicine as
prescribed.
Iron chelation treatment can take time and be mildly painful. However, don't stop taking
your medicine. The leading cause of death among people who have thalassemias is heart
disease caused by iron overload. Iron buildup can damage your heart, liver, and other
organs.
Several chelation treatments are now available, including injections and pills. Your doctor
will talk with you about which treatment is best for you.
Take folic acid supplements if your doctor prescribes them. Folic acid is a B vitamin that
helps build healthy red blood cells. Also, talk with your doctor about whether you need
other vitamin or mineral supplements, such as vitamins A, C, or D or selenium.

Get Ongoing Medical Care

Keep your scheduled medical appointments, and get any tests that your doctor
recommends.
These tests may include:

Monthly complete blood counts and tests for blood iron levels every 3 months
Yearly tests for heart function, liver function, and viral infections (for example,
hepatitis B and C and HIV)
Yearly tests to check for iron buildup in your liver
Yearly vision and hearing tests
Regular checkups to make sure blood transfusions are working
Other tests as needed (such as lung function tests, genetic tests, and tests to match
your tissues with a possible donor if a stem cell transplant is being considered)

Children who have thalassemias should receive yearly checkups to monitor their growth
and development. The checkups include a physical exam, including a height and weight
check, and any necessary tests.

Take Steps To Stay Healthy

Take steps to stay as healthy as possible. Follow a healthy eating plan and your doctor's
instructions for taking iron supplements.
Get vaccinations as needed, especially if you've had your spleen removed. You may need
vaccines for the flu, pneumonia, hepatitis B, and meningitis. Your doctor will advise you
about which vaccines you need.
Watch for signs of infection (such as a fever) and take steps to lower your risk for
infection (especially if you've had your spleen removed). For example:

Wash your hands often.

Avoid crowds during cold and flu season.
Keep the skin around the site where you get blood transfusions as clean as
possible.
Call your doctor if a fever develops.

Emotional Issues and Support

If you or your child has thalassemia, you may have fear, anxiety, depression, or stress.
Talk about how you feel with your health care team. Talking to a professional counselor
also can help. If youre very depressed, your doctor may recommend medicines or other
treatments that can improve your quality of life.

Joining a patient support group may help you adjust to living with thalassemia. You can
see how other people who have the same symptoms have coped with them. Talk with
your doctor about local support groups or check with an area medical center.
Support from family and friends also can help relieve stress and anxiety. Let your loved
ones know how you feel and what they can do to help you.
Some teens and young adults who have thalassemias may have a hard time moving from
pediatric care to adult care. Doctors and other health professionals who care for these
children might not be familiar with adult issues related to the disorder, such as certain
complications.
Also, it might be hard for adults who have thalassemias to find doctors who specialize in
treating the disorder. Ask your child's doctor to help you find a doctor who can care for
your child when the time comes to make the switch. Planning and good communication
can help this move go smoothly.

Clinical Trials
The National Heart, Lung, and Blood Institute (NHLBI) is strongly committed to
supporting research aimed at preventing and treating heart, lung, and blood diseases and
conditions and sleep disorders.
NHLBI-supported research has led to many advances in medical knowledge and care. For
example, this research has uncovered some of the causes of blood disorders, as well as
ways to prevent and treat these disorders.
Many questions remain about blood disorders, including thalassemias. The NHLBI
continues to support research to learn more. For example, NHLBI-sponsored research
includes studies that explore:

Ways to make gene therapy possible for treating people who have thalassemias
How to improve blood and marrow stem cell transplants for people who have
thalassemias and other severe forms of anemia

Much of the NHLBIs research depends on the willingness of volunteers to take part in
clinical trials. Clinical trials test new ways to prevent, diagnose, or treat various diseases
and conditions.
For example, new treatments for a disease or condition (such as medicines, medical
devices, surgeries, or procedures) are tested in volunteers who have the illness. Testing
shows whether a treatment is safe and effective in humans before it is made available for
widespread use.

By taking part in a clinical trial, you can gain access to new treatments before they're
widely available. You also will have the support of a team of health care providers, who
will likely monitor your health closely. Even if you don't directly benefit from the results
of a clinical trial, the information gathered can help others and add to scientific
knowledge.
If you volunteer for a clinical trial, the research will be explained to you in detail. You'll
learn about treatments and tests you may receive, and the benefits and risks they may
pose. You'll also be given a chance to ask questions about the research. This process is
called informed consent.
If you agree to take part in the trial, you'll be asked to sign an informed consent form.
This form is not a contract. You have the right to withdraw from a study at any time, for
any reason. Also, you have the right to learn about new risks or findings that emerge
during the trial.
For more information about clinical trials related to thalassemias, talk with your doctor.
You also can visit the following Web sites to learn more about clinical research and to
search for clinical trials:

http://clinicalresearch.nih.gov

www.clinicaltrials.gov
www.nhlbi.nih.gov/studies/index.htm

www.researchmatch.org

Links to Other Information About

Thalassemias
NHLBI Resources

Anemia (Health Topics)

Iron-Deficiency Anemia (Health Topics)
Blood Transfusion (Health Topics)
Blood and Marrow Stem Cell Transplant (Health Topics)

Non-NHLBI Resources

Anemia

(MedlinePlus)

Thalassemia

(MedlinePlus)

Clinical Trials

Children and Clinical Studies

Clinical Trials (Health Topics)

Current Research
(ClinicalTrials.gov)
NHLBI Clinical Trials

NIH Clinical Research Trials and You

ResearchMatch

(National Institutes of Health)

(funded by the National Institutes of Health)